Effects of tranexamic acid on the activity of glutamate transporter EAAT3.

ABSTRACT:

Background

Tranexamic acid (TXA) is the most widely used hemostatic agent in surgical patients. However, when used in a high dose, it could cause a seizure in the postoperative period. The exact effector mechanism behind the seizure triggering remains unknown. Therefore, the authors investigated the effects of TXA on the activity of glutamate transporter type 3 (excitatory amino acid transporter 3; EAAT3), which is the main neuronal glutamate transporter type.

Methods

EAAT3 was expressed in Xenopus laevis oocytes through mRNA injection. Oocytes were incubated with diluted tranexamic acid for 72 h. Two-electrode voltage clamping was used to measure membrane currents before, during, and after applying 30 µM L-glutamate. Responses were quantified by integrating the current traces and reported in microcoulombs (µC). Results were presented as mean ± SEM.

Results

TXA (30 to 1,000 µM) significantly decreased EAAT3 activity. Our kinetic study showed that V_max was significantly decreased in the TXA group compared with the control group (1.1 ± 0.1 vs. 1.4 ± 0.1 µC, n = 18-23, P = 0.043), but the K_m did not significantly change (12.7 ± 3.9 µM for TXA vs. 12.8 ± 3.8 for control, n = 18-23, P = 0.986).

Conclusions

Our results suggest that TXA attenuates EAAT3 activity, which may explain its proconvulsant effect.

SUBMITTER: Shin HJ 

PROVIDER: S-EPMC7713840 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature